Bevacizumab and Erlotinib or Sorafenib as First-Line Therapy in Treating Patients With Advanced Liver Cancer
A Randomized Open-Label Multi-Institution Phase II Study of the Combination of Bevacizumab and Erlotinib Compared to Sorafenib in the First-Line Treatment of Patients With Advanced Hepatocellular Carcinoma (HCC)
RATIONALE: Monoclonal antibodies, such as bevacizumab, can block tumor growth in different ways. Some block the ability of tumor cells to grow and spread. Others find tumor cells and help kill them or carry tumor-killing substances to them. Erlotinib and sorafenib may stop the growth of tumor cells by blocking some of the enzymes needed for cell growth. Bevacizumab, erlotinib, and sorafenib may also stop the growth of tumor cells by blocking blood flow to the tumor. It is not yet known whether giving bevacizumab together with erlotinib is more effective than giving sorafenib in treating patients with liver cancer.
PURPOSE: This randomized phase II trial is studying how well giving bevacizumab together with erlotinib works compared with sorafenib as first-line therapy in treating patients with advanced liver cancer.
研究概览
详细说明
OBJECTIVES:
Primary
- To estimate the overall survival in patients with advanced hepatocellular carcinoma treated with bevacizumab and erlotinib hydrochloride vs sorafenib tosylate.
Secondary
- To estimate the event-free survival and tumor response rate of these patients.
- To evaluate the safety and tolerability of these regimens in these patients.
OUTLINE: This is a multicenter study. Patients are randomized to 1 of 2 treatment arms.
- Arm I: Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
- Arm II: Patients receive oral sorafenib tosylate twice daily on days 1-28. In both arms, courses repeat every 28 days in the absence of disease progression or unacceptable toxicity.
After completion of study treatment, patients are followed at 30 days and then every 3 months for 1 year.
研究类型
注册 (实际的)
阶段
- 阶段2
联系人和位置
学习地点
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California
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Los Angeles、California、美国、90033-0804
- USC/Norris Comprehensive Cancer Center and Hospital
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San Francisco、California、美国、94115
- California Pacific Medical Center
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New York
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New York、New York、美国、10032
- Columbia University/ New York Presbyterian Hospital
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South Carolina
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Charleston、South Carolina、美国、29425
- Hollings Cancer Center at Medical University of South Carolina
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Tennessee
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Nashville、Tennessee、美国、37203
- Tennessee Oncology, PLLCat Sarah Cannon Cancer Center
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Virginia
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Charlottesville、Virginia、美国、22908
- UVA Cancer Center
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参与标准
资格标准
适合学习的年龄
接受健康志愿者
有资格学习的性别
描述
DISEASE CHARACTERISTICS:
Pathologically confirmed advanced hepatocellular carcinoma (HCC)
- Childs-Pugh class A
- CLIP score ≤ 5
- Not a candidate for curative surgical resection or loco-regional therapy
Measurable disease as per RECIST 1.1 criteria, defined as ≥ 1 previously unirradiated, bidimensionally measurable lesion ≥ 20 mm by CT scan or MRI (triphasic spiral CT scan or MRI employing a "liver protocol" image capture technique required)
- Bone lesions, ascites, and pleural effusions are not considered measurable lesions
- No fibrolamellar HCC
- No known brain metastases
- No prior organ transplantation
PATIENT CHARACTERISTICS:
- ECOG performance status 0-2
- Absolute neutrophil count ≥ 1,500/mm³
- Platelet count ≥ 75,000/mm³
- Hemoglobin ≥ 9 g/dL
- Transaminases ≤ 5 times upper limit of normal (ULN)
- Total bilirubin ≤ 2.0 times ULN
PT ≤ 1.8 times ULN
- Prolonged INR allowed for patients who require full dose anticoagulation
- Creatinine ≤ 2.0 mg/dL OR creatinine clearance ≥ 45 mL/min
- Urine protein < 2+ by urine dipstick OR urine protein ≤ 1 g by 24-hour urine collection
- Not pregnant or nursing
- Negative pregnancy test
- Fertile patients must use effective contraception during and for 12 weeks after completion of study treatment
- Able to take and absorb oral medication
- No active infection requiring parenteral therapy
- No known HIV or AIDS
- No uncontrolled blood pressure (BP), defined as systolic BP ≥ 150 mm Hg and/or diastolic BP ≥ 100 mm Hg
No uncontrolled or significant cardiovascular disease, including any of the following:
- Myocardial infarction within the past 6 months
- Uncontrolled angina within the past 6 months
- New York Heart Association class II-IV congestive heart failure
- Grade 3 cardiac valve dysfunction
- Cardiac arrhythmia not controlled by medication
- Stroke or transient ischemic attack within the past 6 months
- Arterial thrombotic event of any type within the past 6 months
- No significant or symptomatic vascular disease (e.g., aortic aneurysm, aortic dissection, or peripheral vascular disease) within the past 6 months
- No decompensated liver disease as evidenced by clinically significant ascites refractory to diuretic therapy, hepatic encephalopathy, or coagulopathy not corrected by conservative measures
No grade 3 bleeding esophageal or gastric varices within the past 2 months
- Prior variceal bleeding allowed provided patient has undergone banding or sclerotherapy and there has been no evidence of bleeding for 2 months
- No gastric varices ≥ grade 2
- No hemoptysis (i.e., ≥ ½ teaspoon of bright red blood per episode) within the past month
- No evidence of bleeding diathesis or coagulopathy
- No concurrent uncontrolled illness, including, but not limited to, a history of or current evidence of unexplained nephrotic syndrome or other severe illness/disease that would preclude study participation
- No history of hypertensive crisis or hypertensive encephalopathy
- No abdominal fistula, gastrointestinal perforation, or intra-abdominal abscess within the past 6 months
- No serious, non-healing wound, active ulcer, or untreated bone fracture
- No significant traumatic injury within the past 28 days
- No history of allergy to bevacizumab, erlotinib hydrochloride, sorafenib tosylate, or related compounds
- No other primary malignancy within the past 5 years, except carcinoma in situ of the cervix or urinary bladder or nonmelanoma skin cancer
- No mental incapacitation or psychiatric illness that would preclude study participation
- Not incarcerated or compulsorily detained (i.e., involuntarily incarcerated) for treatment of either a psychiatric or physical illness (e.g., infectious disease)
PRIOR CONCURRENT THERAPY:
- Prior surgery, local ablation, trans-arterial hepatic artery embolization, or trans-arterial chemoembolization are allowed provided the lesion(s) have progressed since treatment OR there are additional measurable, untreated lesions present
- No prior systemic therapy for HCC
- No prior organ transplantation
- More than 7 days since prior minor surgical procedures, fine needle aspirations, or core biopsies (excluding placement of a vascular access device)
- More than 28 days since any prior therapy
- More than 28 days since prior and no concurrent major surgical procedure or open biopsy
- More than 28 days since prior and no concurrent participation in another experimental drug study
- No other concurrent anticancer or antitumor therapy, including chemotherapy, radiotherapy, immunotherapy, or hormonal anticancer therapy
- No other concurrent investigational agents
- No concurrent warfarin (other types of anticoagulation allowed)
学习计划
研究是如何设计的?
设计细节
- 主要用途:治疗
- 分配:随机化
- 介入模型:并行分配
- 屏蔽:无(打开标签)
武器和干预
参与者组/臂 |
干预/治疗 |
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实验性的:Arm 1: bevacizumab and erlotinib
Patients receive bevacizumab IV over 30-90 minutes on days 1 and 15 and oral erlotinib hydrochloride once daily on days 1-28.
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鉴于IV
口头给予
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有源比较器:Arm 2: sorafenib tosylate
Patients receive oral sorafenib tosylate twice daily on days 1-28.
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口头给予
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研究衡量的是什么?
主要结果指标
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Overall Survival
大体时间:from date of day 1 until the date of death
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Overall survival is defined as the time from treatment day 1 until death from any cause.
Patients still alive at the end of follow up,patients who withdrew consent from the trial and patients who were lost to follow up will have their survival time censored at the last date of contact.
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from date of day 1 until the date of death
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次要结果测量
结果测量 |
措施说明 |
大体时间 |
---|---|---|
Event-free Survival
大体时间:From the time of randomization until progression, withdrawal due to toxicity or any other clinical event requiring withdrawal from the study.
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EFS is defined as the time from randomization to any of the following three types of events: 1 - progression; 2 - withdrawal due to excessive toxicity; 3 - any other clinical event requiring withdrawal from the study.
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From the time of randomization until progression, withdrawal due to toxicity or any other clinical event requiring withdrawal from the study.
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Number of SAEs Experienced
大体时间:From day 1 of drug administration until 30 days after the last dose of study drug.
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The study will report the number of SAEs experienced in each arm.
All patients who receive any study drug will be evaluable for toxicity.
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From day 1 of drug administration until 30 days after the last dose of study drug.
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Response Rate
大体时间:From day 1 drug administration until 30 days after the last dose of study drug.
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Secondary outcome measures include response rate as assessed on restaging imaging studies utilizing RECIST 1.1.
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From day 1 drug administration until 30 days after the last dose of study drug.
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合作者和调查者
研究记录日期
研究主要日期
学习开始
初级完成 (实际的)
研究完成 (实际的)
研究注册日期
首次提交
首先提交符合 QC 标准的
首次发布 (估计)
研究记录更新
最后更新发布 (实际的)
上次提交的符合 QC 标准的更新
最后验证
更多信息
此信息直接从 clinicaltrials.gov 网站检索,没有任何更改。如果您有任何更改、删除或更新研究详细信息的请求,请联系 register@clinicaltrials.gov. clinicaltrials.gov 上实施更改,我们的网站上也会自动更新.
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